Systemic lupus erythematosus (SLE) is an autoimmune disease triggered by a complex interaction of immunologic, environmental, and genetic factors. Like other diseases of autoimmune origin, SLE manifestations follow relapsing and remitting courses. Several lines of evidence have demonstrated the association of adaptive and innate immune responses with regulation in SLE pathogenesis. The immunological diagnosis primarily relies on detection of serum autoantibodies in SLE patients. A concordance rate of < 25% between monozygotic twins indicates potential involvement of environmental factors in SLE development. In addition, SLE is categorized by a wide range of clinical manifestations, partly related to the disease itself but also associated with comorbidities and adverse drug reactions. Because the common therapeutic strategies are connected with certain adverse events, immunosuppressive medications and biological agents are used on the basis of prevailing disease manifestations. Genome-wide association studies have identified 50 loci that influence SLE. However, the actual genetic polymorphism that imparts SLE risk is not fully known. Further understanding can help to expand quality of life in SLE individuals.